The right bond in the right place

Enzymes excel at specificity because of their constrained active sites. With appropriate evolutionary pressure, they can be made to differentiate between similar substrates or between positions on a single substrate. Cho et al. used directed evolution to generate cytochrome P450 variants that target different C–H bonds in substrates, forming lactam rings of varying size (see the Perspective by Hepworth and Flitsch). The enzyme directs amidation to the desired position and simultaneously prevents other side reactions.